The Korean Journal of Pain

The Korean Pain Society (대한통증학회)
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Intrathecal administration of naringenin improves motor dysfunction and neuropathic pain following compression spinal cord injury in rats: relevance to its antioxidant and anti-inflammatory activities

  • Fakhri, Sajad (Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences) ;
  • Sabouri, Shahryar (Student Research Committee, Kermanshah University of Medical Sciences) ;
  • Kiani, Amir (Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences) ;
  • Farzaei, Mohammad Hosein (Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences) ;
  • Rashidi, Khodabakhsh (Research Center of Oils and Fats, Kermanshah University of Medical Sciences) ;
  • Mohammadi-Farani, Ahmad (Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences) ;
  • Mohammadi-Noori, Ehsan (Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences) ;
  • Abbaszadeh, Fatemeh (Department of Neuroscience, Faculty of Advanced Technologies in Medical Sciences, Iran University of Medical Sciences)
  • Received : 2022.03.28
  • Accepted : 2022.05.13
  • Published : 2022.07.01
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Abstract

Background: Spinal cord injury (SCI) is one of the most debilitating disorders throughout the world, causing persistent sensory-motor dysfunction, with no effective treatment. Oxidative stress and inflammatory responses play key roles in the secondary phase of SCI. Naringenin (NAR) is a natural flavonoid with known anti-inflammatory and antioxidative properties. This study aims at evaluating the effects of intrathecal NAR administration on sensory-motor disability after SCI. Methods: Animals underwent a severe compression injury using an aneurysm clip. About 30 minutes after surgery, NAR was injected intrathecally at the doses of 5, 10, and 15 mM in 20 µL volumes. For the assessment of neuropathic pain and locomotor function, acetone drop, hot plate, inclined plane, and Basso, Beattie, Bresnahan tests were carried out weekly till day 28 post-SCI. Effects of NAR on matrix metalloproteinase (MMP)-2 and MMP-9 activity was appraised by gelatin zymography. Also, histopathological analyses and serum levels of glutathione (GSH), catalase and nitrite were measured in different groups. Results: NAR reduced neuropathic pain, improved locomotor function, and also attenuated SCI-induced weight loss weekly till day 28 post-SCI. Zymography analysis showed that NAR suppressed MMP-9 activity, whereas it increased that of MMP-2, indicating its anti-neuroinflammatory effects. Also, intrathecal NAR modified oxidative stress related markers GSH, catalase, and nitrite levels. Besides, the neuroprotective effect of NAR was corroborated through increased survival of sensory and motor neurons after SCI. Conclusions: These results suggest intrathecal NAR as a promising candidate for medical therapeutics for SCI-induced sensory and motor dysfunction.

Keywords

Acknowledgement

The authors acknowledged Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, for the special Grant No. 4000170.

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